It is known that certain mevalonate derivatives inhibit the biosynthesis of cholesterol, cf. F. M. Singer et al, Proc. Soc. Exper. Biol. Med., 102, 370 (1959) and F. H. Hulcher, Arch. Biochem. Biophys., 146, 422 (1971). Nevertheless, the activity of these known compounds has not always been found to be satisfactory, i.e. to have practical application.
Recently, Endo et al, reported (U.S. Pat. No. 4,049,495, U.S. Pat. No. 4,137,322 and U.S. Pat. No. 3,983,140) the production of fermentation products which were quite active in the inhibition of cholesterol biosynthesis. This natural product, now called Compactin, was reported by Brown et al (J. Chem. Soc. Perkin I 1165 (1976)) to have a complex mevalonolactone structure.
More recently Monaghan et al in U.S. Ser. No. 048,946, filed June 15, 1979, now U.S. Pat. No. 4,231,938, which is incorporated herein by reference, reported an even more potent inhibitor, having the structure III.sub.a in Table I isolated from an entirely different fermentation. Albers-Schonberg et al (U.S. Ser. No. 154,157, filed May 28, 1980) described a dihydro-III.sub.a designated Compound III.sub.d of equal potency isolated from the same fermentation.
Patchett et al (U.S. Ser. No. 118,050, filed Feb. 4, 1980) describe dihydro and tetrahydro derivatives of III.sub.a with structures of Compounds III.sub.b,c,e prepared by the catalytic hydrogenation of III.sub.a.
The preparation of the starting material, III.sub.d, as mentioned previously, is described by Albers-Schonberg et al in U.S. application, Ser. No. 154,157, filed May 28, 1980 and is a product of the following fermentation with a strain of Aspergillus terreus, ATCC No. 20542, designated MF-4845 in the culture collection of Merck & Co., Inc., Rahway, N.J.